Composition comprising an extract of hardy kiwi for preventing or treating baldness disorders or seborrheic skin disorders

ABSTRACT

Provided is a use of a crude extract, non-polar solvent soluble extract or purified extract of the hardy kiwifruit for the preparation of therapeutic agent for treating and preventing baldness disorder and seborrheic skin disease in human and mammal, and health care food, food additives, feed additives, cosmetic composition comprising the same. The hardy kiwifruit reduced blood DHT level, promoted the formation of hair root in mouse model experiment, and inhibited the falling out of hair and improved seborrheic skin disease of volunteers such as keratigenous skin, seborrhea etc.

This application is a continuation application of U.S. application Ser.No. 12/868,130 (now allowed) filed on Aug. 25, 2010, which is acontinuation-in-part application of U.S. application Ser. No. 11/573,445filed on Feb. 8, 2007, which is a national stage application under 35U.S.C. §371 of PCT/KR2004/002010 filed on Aug. 10, 2004, the disclosuresof which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention relates to a composition comprising an extract ofhardy kiwi having preventing, improving or treating activity of baldnessdisorder or seborrheic skin disease.

2. Background Art

The present invention relates to a composition comprising the extract ofhardy kiwi having ability of preventing and treating on baldness diseaseor seborrheic skin disease, and especially, a composition comprising acrude extract, non-polar solvent soluble extract, or purified fractionof hardy kiwi extract for the prevention or treatment of baldnessdisease or seborrheic skin disease.

Baldness syndrome is frequently occurred in middle-aged male andclassified into two types of baldness. One is male pattern baldnessalternatively named as an alopecia seniles or androgenic alopeciagenerally occurred in the forehead or calvaria of middle-aged male, andanother is alopecia areata which shows relatively concrete border lineof alopecia and frequently being occurred in juvenile person. Thesyndrome is mainly occurred in male and even in female (M. Inaba et al;Androgenetic alopecia, Springer-Berlag, Tokyo, Japan, 1996).

There has been reported that alopecia is originated from genetic factor,the progress of aging, drug abuse, radioactive treatment and the stressoccurred after serious illness etc. It has been known that main factorsof alopecia are over-production of androgenic hormone, blood circulationproblem in scalp, and deficiency of essential vitamins to hairmetabolism in biochemical and physiological aspects. The main factor ofmale pattern baldness relates to androgen and steroid hormones, inparticular, 5-α-reductase which is converting testosterone to5-α-dihydrotestosterone (DHT) and which is distributed in sebaceousgland, keratinocytes of hair follicle, dermal papilla cell, sweat gland,root sheath of the scalp hair follicle and aromatase which is convertingandrogen to female hormone such as estradiol. The etiological origin ofalopecia areata is known to be the disorder of autoimmune system,especially the lymphocyte CD4+ disorder in melanocyte, keratinocyte,dermal papilla and vascular endothelium (J. Shapiro et al; Therapeuticagents, Dermatol. Clin., 16(2) pp 341-356, 1998).

Various conventional drugs for the treatment of alopecia have beendeveloped till now. Finasteride, an oral 5-α-reductase inhibitor, isavailable in the market, however it has several disadvantages such asrecurrence at cease of administration, usage limitation in pregnantwomen, and sexual dysfunction upon long-term administration; minoxidilhas been used to treat male pattern baldness combined with other agentssuch as cell division accelerator, vasodilator, capillary formationpromotor, immuno-suppressor, cAMP modulator, EGF (epithelial cell growthfactor), and cell proliferation modulator. However it also has adverseeffects such as repetitive recurrence and rapid reduction of bloodpressure at cease of administration too. ACTH (adrenocorticotrophin) animmuno-modulating agent acting on limphocyte to suppress hyperactiveimmune system has been administrated to treat alopecia areata in formsof ointment or in injection formulations. However it also has severaldisadvantages including recurrence and adverse effects upon long termadministration. Besides the described drugs, cyproterone actate,spironolactone or estrogen have been reported to treat alopecia (J.Shapiro et al, Hair regrowth, Therapeutic agents, Dermatol. Clin. 16(2),pp 341-356, 1998)

Most of them do not provide enough efficacy to accomplish a satisfactoryactivity and have several disadvantages including recurrence and adverseeffects. Therefore there have been demands for a new drug which provideswith satisfactory effect and reduced adverse effect till now.

Meanwhile, there have been various approaches to develop an effectivedrug from natural resources to treat and to prevent alopecia.

As an alternative approach, there have been several reports on acomposition comprising an extract of natural product having hair growthstimulating effect, for example, 1) an extract belonged to Orchidaceaedisclosed in Korea Patent Registration No. 015667; 2) vitex seed andbear fat in Korea Patent Registration No. 0161338; 3) an extract ofRhododendron fauriae in Korea Patent Publication No. 91-106; 4) pineleaf extract in Korea Patent Publication No. 96-40346; 5) a crudeextract of torilla seed, pine leaf and silkworm moth in Korea PatentPublication No. 90-2757; 6) a crude extract of Acanthopanaxsessiliflorus, Astragalus membranceus, Polygonum multiflorum, Dioscoreanipponica and Fagopyrum esculentum in Korea Patent Publication No.2000-24499; 7) a crude extract of Pinellia ternata, EugeniaCaryophyllata, Rubus coreanus, Zanthoxylum piperatum, Vitexrotundifolia, Salvia miltiorrhiza, and Thujae semen in Korea PatentRegistration No. 259037; 8) the fat obtained by heating silkworm andtheir byproduct, at 200° C. for 15 mins, an extract of one or more ofPanax ginseng, Angelica sinensis, Astragalus membranceus, Polygonummultiflorum, Juglans sinensis, Rubus coreanus, Rehmannia glustinosa,Psoralea corylifolia, Pinus densiflora, Vitex rotundifolia, Carthamustinctorius and Ligustrum lucidum in Korea Patent Publication No.90-13934; 9) an extract of one or more of silkworm moth, silkworm eggs,silkworm pupa, black sesame seeds, sesame seeds, brown seaweed, andwalnuts in Korea Patent Publication No. 90-5952; 10) mixed powder ofmung beans, soy bean, perilla seeds, sesame seeds, walnuts, laver, seamussel, oyster, anchovy, brown seaweed, and yeast concentrates in KoreaPatent Registration No. 260673; and 11) an extract of fruits, root,branch, leaf, flowers of Lycium chinensis, and corn silk in Korea PatentPublication No. 2000-36534. However, the hair growing effect of theabove described composition disclosed therein have not been fullysupported or identified in any of the disclosure.

More than 30 species belonged to Actinidiaceae have been reported.Actinidia arguta, A. polygama and A. omikta belonged to Actinidiaceae,are distributed in Siberia, the northern area of China, North and SouthKorea. Actinidia arguta, A. polygama and A. kolomikta have been used asmaterials of traditional oriental medicine named as ‘mihudo’, to treatliver disease, gastrointestinal disease and urogenital lithiasis withouttoxicity (Chung B. S. and Shin M. K.; HyangyakDaesacheon, Youngrimsa.,pp 386-388, 1998).

Meanwhile, there have been several applications regarding the activityof Actinidia fruit to treat or prevent various medicinal diseases tillnow.

For example, Korea Patent Publication No. 2002-78467 discloses healthbeverage containing an extract of crude drugs consisting of Actinidiaarguta, Hovenia dulcis, Lycium chinensis, Schizandra chinensis, Artemiscapillaries, Pueraria thunbergiana, Glycyrrhiza uralensis, Lagenariasiceraria, Aralia elata, Polygala tenuifolia, Angelica sinensis,Atractylodes macrocephala, Gardenia jasminoides, Astragalusmembranaceus, Carthamus tinctorius and Cordyceps militaris for theimprovement of liver function.

However, there has been not reported or disclosed an activity of anextract of hardy kiwi for treating or preventing alopecia and seborrheicskin disease in any of above literatures.

To investigate the treating or preventing effect of hardy kiwi extracton alopecia and seborrheic skin disease, the inventors of the inventionhave intensively carried out in vivo and in vitro experiment concerningthe inhibition effect on the reproduction of DHT (dihydrotestosterone)together with clinical experiment concerning on the hair growthstimulation and seborrheic skin disease. As a result of theinvestigation, the inventors finally confirm that the extract of hardykiwi reduced blood DHT level, and inhibited the falling out of hair aswell as suppressed the severity of seborrheic skin disease.

SUMMARY OF THE INVENTION

The present invention provides a pharmaceutical composition comprisingan extract of hardy kiwi as an active ingredient in an effective amountto treat or prevent baldness disorder or seborrheic skin disease.

The present invention provides a use of an extract of hardy kiwi for thepreparation of pharmaceutical composition for to preventing oralleviating baldness disorder or seborrheic skin disease in human ormammal.

The present invention also provides a method for treatment, improvementor prevention of baldness disorder or seborrheic skin disease in amammal comprising administering to said mammal an effective amount of acrude extract, non-polar solvent soluble extract or purified extract ofhardy kiwi, together with a pharmaceutically acceptable carrier thereof.

The present invention also provides a health food or food additivescomprising an extract of hardy kiwi for improvement or prevention ofbaldness disorder or seborrheic skin disease.

The present invention also provides a feed or feed additive comprisingan extract of hardy kiwi for treatment or prevention of baldnessdisorder or seborrheic skin disease.

The present invention also provides a cosmetic composition comprising anextract of hardy kiwi as an active ingredient in an effective amount totreat or prevent baldness disorder or seborrheic skin disease.

DISCLOSURE OF THE INVENTION

Accordingly, it is an object of the present invention to provide apharmaceutical composition comprising a crude extract, non-polar solventsoluble extract or purified extract of hardy kiwi as an activeingredients for treatment or prevention of baldness disorder orseborrheic skin disease.

It is an object of the present invention to provide a use of a crudeextract, non-polar solvent soluble extract or purified extract of hardykiwi for the preparation of a therapeutic agent for treating orpreventing baldness disorder or seborrheic skin disease in human ormammal.

It is an object of the present invention to provide a method fortreatment, improvement or prevention of baldness disorder or seborrheicskin disease in a mammal comprising administering to said mammal aneffective amount of a crude extract, non-polar solvent soluble extractor purified extract of hardy kiwi, together with a pharmaceuticallyacceptable carrier thereof.

It is another object of the present invention to provide a health foodor food additives comprising the above described extract, together witha sitologically acceptable additive for prevention, treatment orimprovement of baldness disorder or seborrheic skin disease.

It is still another object of the present invention to provide a feed orfeed additive comprising the above described extract as essentialcomponents for treatment, prevention, or improvement of baldnessdisorder or seborrheic skin disease.

It is still another object of the present invention to provide acosmetic composition comprising the described extract for prevention,treatment or improvement of baldness disorder or seborrheic skindisease.

Above described baldness disorders herein comprise alopecia seniles,alopecia areata and the like.

The term “crude extract” defined herein means “an extract” soluble inwater, lower alcohol such as methanol, ethanol, butanol or a mixturethereof, preferably, an organic solvent mixture mixed with water andethanol.

Preferably, the above described crude extract herein comprises anextract obtained by the step consisting of: extracting hardy kiwi withwater, lower alcohol such as methanol, ethanol or butanol and themixture thereof, preferably, an organic solvent mixture mixed with waterand ethanol; filtrating and concentrating the filtrate.

The term “non-polar solvent soluble extract” defined herein means “anextract” soluble in chloroform, ethylacetate, hexane, dichloromethane orether, preferably, ethylactate.

Above described non-polar soluble extract herein comprises an extractobtained by the step consisting of: extracting hardy kiwi with anon-polar solvent such as chloroform, ethylacetate, hexane,dichloromethane or ether, preferably, ethylactate; filtrating andconcentrating the filtrate.

The term “hardy kiwi” defined herein means any of “plants with hairlessfruits” belonged to Actinidia genus.

Above hardy kiwi may comprise Actinidia arguta, A. kolomikta or A.polygama (Strik et al., Journal of the American Pomological Society,2006) and may use the fruit, stem, root thereof.

The pharmaceutical composition of the present invention can containabout 0.01 to 50% by weight of the above extract based on the totalweight of the composition.

The health food of the present invention comprises above extracts as0.01 to 95%, preferably 1 to 80% by weight based on the total weight ofthe composition.

Above health food can be contained in health food, health beverage etc,and may be used as powder, granule, tablet, chewing tablet, capsule,beverage etc.

An inventive extract from hardy kiwi may be prepared in accordance withthe following preferred embodiment.

Hereinafter, the present invention is described in detail.

An inventive extract of hardy kiwi can be prepared in detail byfollowing procedures,

The inventive crude extract of hardy kiwi can be prepared by follows;hardy kiwi is dried, cut, crushed and mixed with 2 to 25-fold,preferably, approximately 10 fold volume of distilled water, loweralcohols such as methanol, ethanol, butanol and the like, or themixtures thereof, preferably ethanol; the solution is treated with hotwater at the temperature ranging from 20 to 100° C., preferably from 60to 100° C., for the period ranging from 1 to 24 hours with extractionmethod by the extraction with hot water, cold water, reflux extraction,or ultra-sonication extraction with 1 to 5 times, preferably 2 to 3times, consecutively; the residue is filtered to obtain the supernatantto be concentrated with rotary evaporator, at the temperature rangingfrom 20 to 100° C., preferably from 50 to 70° C. and then dried byvacuum freeze-drying, hot air-drying or spray drying to obtain driedcrude extract powder of hardy kiwi which can be soluble in water, loweralcohols, or the mixtures thereof.

Additionally, polar solvent soluble and non-polar solvent solubleextract of present invention can be prepared by following procedure; thecrude extract prepared by above step, is suspended in water, and then ismixed with 1 to 100-fold, preferably, 1 to 5-fold volume of non polarsolvent such as ethyl acetate, chloroform, hexane and the like; thenon-polar solvent soluble layer is collected to obtain non-polar solventsoluble extract of the present invention and remaining polar solventsoluble layer is collected to obtain polar solvent soluble extract ofthe present invention which is soluble in water, lower alcohols, or themixtures thereof. Also, above described procedures may be modified orsubjected to further step to fractionate or isolate more potentfractions or compounds by conventional procedure well known in the art,i.e., the procedure disclosed in the literature (Harborne J. B.Phytochemical methods: A guide to modern techniques of plant analysis,3^(rd) Ed. pp 6-7, 1998).

For example, the further purified fractions from the extract of hardykiwi in the present invention can be prepared by subjecting non-polarsolvent soluble extract prepared by aforementioned step to columnchromatographic process such as Silicagel column chromatography, TLC(Thin layer chromatography) or Sephadex column chromatography,preferably, Silicagel column chromatography eluting with eluting solventmixed with chloroform:methanol:water in order to increasing theirpolarity in stepwise manner, more preferably, starting with mixed ratioof 100:10:1 (W/W/W) and ending with 20:10:0.5 (W/W/W) to obtain furtherpurified extract, in particular, the purified extracts having TLCspectra as shown in FIGS. 1 to 3.

Accordingly, the present invention to also provide a pharmaceuticalcomposition comprising the crude extract, non-polar solvent solubleextract or purified extract of the hardy kiwi obtained by abovedescribed method as an active ingredients for treatment or prevention ofbaldness disorder or seborrheic skin disease.

It is an object of the present invention to provide a use of the crudeextract, non-polar solvent soluble extract or purified extract of hardykiwi obtained by above described method for the preparation oftherapeutic agent for treating or preventing baldness disorder orseborrheic skin disease in human or mammal.

The term “purified extract” defined herein means any of “fractions”obtained by column chromatographic purification having more potentactivity than that of polar or non-polar solvent soluble extracts,preferably, the purified extracts having TLC spectra as shown in FIGS. 1to 3.

To investigate the inhibiting activity of the crude extract, non-polarsolvent soluble extracts and purified extracts of hardy kiwi extractprepared by above procedure on the baldness disorder or seborrheic skindisease, in vivo and in vitro experiments concerning the inhibitioneffect on the reproduction of DHT (dihydrotestosterone) in mouse bloodand on the formation of mouse hair root together with clinicalexperiment concerning on the hair growth stimulation and seborrheic skindisease were carried out. As a result of the investigation, theinventors confirmed that an orally administrated hardy kiwi extractreduced blood DHT level, promoted the formation of hair root in mousemodel experiment, and inhibited the falling out of hair and improvedseborrheic skin disease of volunteers such as keratic skin, seborrheaetc.

In accordance with another aspect of the present invention, there isprovided a pharmaceutical composition comprising the extract of hardykiwi prepared by above preparation method for the treatment orprevention of baldness disorder or seborrheic skin disease as activeingredients.

It is another of the present invention to provide a treating method orpreventing method comprising administering a pharmaceutical compositioncomprising said extract prepared by above preparation method to human ormammals suffering from baldness disorder or seborrheic skin disease.

The composition for treating or preventing baldness disorder andseborrheic skin disease may comprises above extracts as 0.01 to 50% byweight based on the total weight of the composition.

The inventive composition may additionally comprise a conventionalcarrier, adjuvant or diluents in accordance with conventional usingmethod well known in the art.

Hereinafter, the following formulation methods and excipients are merelyexemplary and in no way limit the invention.

The composition according to the present invention can be provided as apharmaceutical composition containing pharmaceutically acceptablecarriers, adjuvants or diluents, e.g., lactose, dextrose, sucrose,sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acaciarubber, alginate, gelatin, calcium phosphate, calcium silicate,cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxy benzoate, talc, magnesium stearate and mineraloil. The formulations may additionally include fillers,anti-agglutinating agents, lubricating agents, wetting agents, flavoringagents, emulsifiers, preservatives and the like. The compositions of theinvention may be formulated so as to provide quick, sustained or delayedrelease of the active ingredient after their administration to a patientby employing any of the procedures well known in the art.

For example, the compositions of the present invention can be dissolvedin oils, propylene glycol or other solvents that are commonly used toproduce an injection. Suitable examples of the carriers includephysiological saline, polyethylene glycol, ethanol, vegetable oils,isopropyl myristate, etc., but are not limited to them. For topicaladministration, the compounds of the present invention can be formulatedin the form of ointments or creams.

Pharmaceutical formulations containing the composition of the inventionmay be prepared in any form, such as oral dosage form (powder, tablet,capsule, soft capsule, aqueous medicine, syrup, elixirs pill, powder,sachet, granule), or topical preparation (cream, ointment, lotion, gel,balm, patch, paste, spray solution, aerosol and the like), or injectablepreparation (solution, suspension, emulsion).

The composition of the present invention in pharmaceutical dosage formsmay be used in the form of their pharmaceutically acceptable salts, andalso may be used alone or in appropriate association, as well as incombination with other pharmaceutically active compounds.

The desirable dose of the inventive extract or composition variesdepending on the condition and the weight of the subject, severity, drugform, route and period of administration, and may be chosen by thoseskilled in the art. However, in order to obtain desirable effects, it isgenerally recommended to administer at the amount ranging 0.01 to 10g/kg, preferably, 0.1 to 3 g/kg by weight/day of the inventive extractor compounds of the present invention. The dose may be administered insingle or divided into several times per day. In terms of composition,the amount of inventive extract should be present between 0.01 to 95% byweight, preferably 0.5 to 80% by weight based on the total weight of thecomposition.

The pharmaceutical composition of present invention can be administeredto a subject animal such as mammals (rat, mouse, domestic animals orhuman) via various routes. All modes of administration are contemplated,for example, administration can be made orally, rectally or byintravenous, intramuscular, subcutaneous, intracutaneous, intrathecal,epidural or intracerebroventricular injection.

Also, the present invention provide a composition of the health foodbeverage for prevention or improvement of baldness disorder orseborrheic skin disease adding the extract of hardy kiwi 0.01 to 20% byweight, amino acids 0.001 to 5% by weight, vitamins 0.001 to 2% byweight, sugars 0.001 to 20% by weight, organic acids 0.001 to 10% byweight, sweetener and flavors of proper amount.

Above the extract of hardy kiwi can be added to food or beverage for theprevention or improvement of baldness disorder or seborrheic skindisease.

To develop for health food, examples of addable food comprising aboveextracts of the present invention are e.g., various food, beverage, gum,vitamin complex, health improving food and the like, and can be used aspower, granule, tablet, chewing tablet, capsule or beverage etc.

Also, the extract of present invention will be able to prevent orimprove baldness disorder and seborrheic skin disease by comprising tochild and infant food, such as modified milk powder, modified milkpowder for growth period, modified food for growth period.

Above described composition therein can be added to food, additive orbeverage, wherein, the amount of above described extract in food orbeverage may generally range from about 0.1 to 95 w/w %, preferably 1 to80 w/w % of total weight of food for the health food composition and 1to 30 g, preferably 3 to 10 g on the ratio of 100 ml of the healthbeverage composition.

Providing that the health beverage composition of present inventioncontains above described extract as an essential component in theindicated ratio, there is no particular limitation on the other liquidcomponent, wherein the other component can be various deodorant ornatural carbohydrate etc such as conventional beverage. Examples ofaforementioned natural carbohydrate are monosaccharide such as glucose,fructose etc; disaccharide such as maltose, sucrose etc; conventionalsugar such as dextrin, cyclodextrin; and sugar alcohol such as xylitol,and erythritol etc. As the other deodorant than aforementioned ones,natural deodorant such as taumatin, stevia extract such as levaudiosideA, glycyrrhizin et al., and synthetic deodorant such as saccharin,aspartam et al., may be useful favorably. The amount of above describednatural carbohydrate is generally ranges from about 1 to 20 g,preferably 5 to 12 g in the ratio of 100 ml of present beveragecomposition.

The other components than aforementioned composition are variousnutrients, a vitamin, a mineral or an electrolyte, synthetic flavoringagent, a coloring agent and improving agent in case of cheese chocolateet al., pectic acid and the salt thereof, alginic acid and the saltthereof, organic acid, protective colloidal adhesive, pH controllingagent, stabilizer, a preservative, glycerin, alcohol, carbonizing agentused in carbonate beverage et al. The other component thanaforementioned ones may be fruit juice for preparing natural fruitjuice, fruit juice beverage and vegetable beverage, wherein thecomponent can be used independently or in combination. The ratio of thecomponents is not so important but is generally range from about 0 to 20w/w % per 100 w/w % present composition. Examples of addable foodcomprising aforementioned extract therein are various food, beverage,gum, vitamin complex, health improving food and the like.

The inventive composition may additionally comprise one or more than oneof organic acid, such as citric acid, fumaric acid, adipic acid, lacticacid, malic acid; phosphate, such as phosphate, sodium phosphate,potassium phosphate, acid pyrophosphate, polyphosphate; naturalanti-oxidants, such as polyphenol, catechin, α-tocopherol, rosemaryextract, vitamin C, green tea extract, licorice root extract, chitosan,tannic acid, phytic acid etc.

The above extract of hardy kiwi may be 20 to 90% high concentratedliquid, power, or granule.

Similarly, the above extract of hardy kiwi can comprise additionally oneor more than one of lactose, casein, dextrose, glucose, sucrose andsorbitol.

Also, in the present invention, there is also provided a using method ofthe food additives such as sterilizer, spice, seasoning, variousnutrients, vitamin, a mineral or an electrolyte, synthetic flavoringagent, a coloring agent and improving agent in case of cheese chocolateet al., pectic acid and the salt thereof, alginic acid and the saltthereof, organic acid, protective colloidal adhesive, pH controllingagent, stabilizer, a preservative, glycerin, alcohol, carbonizing agentused in carbonate beverage et al, or as essential component of foodmaterials.

Wherein the food additives can be added to food by deposition, spray, ormixing the ratio of the additives is not so important but is generallyrange from about 0.01 to 20 w/w % per 100 w/w % present composition.Examples of addable food comprising aforementioned extract therein are.

Wherein the food additives can be added to one or one over food such asfruits, vegetables, food dehydrated foods or cutting products such asfruits, vegetables; fruit juice, vegetable juices or the mixture juicesthereof; drinks containing acid-beverage; confectionaries such ascookie, candy, caramel, gum; breads; ice creams, teas, fermented milksuch as yogurt; dairy product, spices, alcoholic beverages, cans,in-bottles, noodles, processed livestock products, processed marineproducts, fermented food, beans food, cereals food, processed meats,licorices or hubs.

In accordance with another aspect of the present invention, there areprovided a feed or feed additive essentially comprising said extractprepared by above preparation method for prevention or improvementbaldness disorder or seborrheic skin disease.

Above food additives of the present invention can be mixed with mixingamount of 5 to 100 g per 1 kg by weight based on the total dried weightof the feed.

Furthermore, the present invention provides a feed compositioncomprising above feed additives.

Also, the present invention also provides a cosmetic compositioncomprising an effective amount of the crude extract or non-polar solventsoluble extract of hardy kiwi for prevention or improvement of baldnessdisorder or seborrheic skin disease.

The present cosmetic composition provide cosmetic composition comprisingthe above extracts with 0.01 to 30%, more preferably, 0.01 to 5% by theweight of the inventive composition based on the total weight of thecomposition for the treatment, prevention or improvement of baldnessdisorder or seborrheic skin disease.

The other components may be a mixture of the ingredients of aconventional cosmetic composition well known in the art.

Cosmetic formulations containing above composition may be prepared inany form such as skin, lotion, cream, essence, toner, emulsion, pack,soup, shampoo, rinse, cleanser, body washing solution, washing solution,treatment, gel, balm, spray solution and the like.

The cosmetic composition of the present invention can comprisesadditional additives selected from the group consisting of water solublevitamin, lipid soluble vitamin, peptide polymer, polysaccharide polymer,sphingolipid and sea-weed extract.

Preferable water soluble vitamins are any one which can be mixed withcosmetic, however, various vitamin such as vitamin B1, B2, B6,pyridoxine, pyridoxine HCl, vitamin B12, pantothenic acid, nicotinicacid, nicotinamide, folic acid, vitamin C, vitamin H etc, their saltthereof such as thiamin HCl salt, ascorbic acid Na salt etc or theirderivatives thereof such as ascorbic acid-2-phosphonic acid Na salt,ascorbic acid-2-phosphonic acid Mg salt are preferable and those can beobtained by conventional method such as microbial conversion method,purification method from the microbial cultivates, enzymatic method orchemical synthetic method.

Preferable lipid soluble vitamins are any one which can be mixed withcosmetic, however, various vitamin such as vitamin A, D2, D3, E(dl-α-tocopherol, d-α-tocopherol, d-δ-tocopherol) and their derivativessuch as palmitic acid ascorbate, stearic acid ascorbate, dipalmitic acidascorbate, acetic acid-dl-α-tocopherol, nicotinic acid dl-α-tocopherolvitamin E, dl-pantothenyl alcohol, D-pantothenyl alcohol, pantothenylethylether etc. containing the lipid soluble vitamin used in examples ofpresent invention are preferable and those can be obtained byconventional method such as microbial conversion method, purificationmethod from the microbial cultivates, enzymatic method or chemicalsynthetic method.

Preferable peptide polymers are any one which can be mixed withcosmetic, however, collagen, hydrolysable collagen, gelatin, elastin,hydrolysable gelatin, keratin etc. containing the peptide polymer usedin examples of present invention are preferable.

Preferable polysaccharide polymers are any one which can be mixed withcosmetic, however, hydroxy ethyl cellulose, xanthin gum, hyaluronic acidNa, chondroitin sulfate or their salt (Na salt etc) and the like arepreferable. For example, chondroitin sulfate or the salt thereof etc canbe used by being purified from mammal or fishes ordinarily.

Preferable sphingolipids are any one, which can be mixed with cosmetic,however, ceramide, pit-sphingosin, sphingo-lipopolysaccharide and thelike are preferable. Sphingo-lipid can be obtained by being purifiedfrom mammal, fish, shellfish, yeast or plant etc in conventional method.

Preferable seaweed extract is any one which can be mixed with cosmetic,however, the extract of brown algae, red algae, green algae and the likeor the purified carrageenan, alginic acid, arginic acid Na, K isolatedtherefrom are preferable. Algae extract can be obtained by beingpurified from seaweed in conventional method.

The cosmetic composition of the present invention may combine with otheringredients combined with conventional cosmetic composition, ifnecessary, together with above described essential ingredient.

The above described other ingredients may comprises oil ingredient,humectants, emollients, surface active agents, organic or inorganic dye,organic powder, ultraviolet ray absorbing agent, preservatives,antiseptics, antioxidants, plant extract, pH controller, alcohol,pigments, perfumes, refrigerants, blood circulator, antihidrotic,distilled water etc.

Preferable oil ingredients may comprise ester oil, hydrocarbon oil,silicone oil, fluoride oil, animal oil, plant oil and so on.

Preferable ester oil described above may comprise glyceryl tri-2-ethylhexanoic acid, cetyl 2-ethyl hexanoic acid, isopropyl myristic acid,butyl myristic acid, isopropyl palmitic acid, ethyl stearic acid, octylpalmitic acid, isocetyl isostearic acid, butyl stearic acid, ethyllinoleic acid, isopropyl linoleic acid, ethyl oleic acid, isocetylmyristic acid, isostearyl myristic acid, isostearyl palmitic acid,octyldodecyl myristic acid, isocetyl isostearic acid, diethyl sebasicacid, isopropyl adipic acid, isoalkyl neopetanoic acid, glyceryltri(capryl, capric acid), trimethylopropane tri-2-ethyl hexanoic acid,trimethylopropane triisostearic acid, pentaerythritol tetra-2 ethylhexanoic acid, cetyl caprylic acid, decyl lauric acid, hexyl lauricacid, decyl myristic acid, myristyl myristic acid, cetyl myristic acid,stearyl stearic acid, decyl oleic acid, cetyl licinoleic acid,isostearyl lauric acid, isotridecyl myristic acid, isocetyl palmiticacid, octyl stearic acid, isocetyl stearic acid, isodecyl oleic acid,octyldodecyl oleic acid, octyldodecyl linoleic acid, isopropylisostearic acid, cetostearyl 2-ethyl hexanoic acid, stearyl 2-ethylhexanoic acid, hexyl isostearic acid, ethylene glycol dioctanoic acid,ethylene glycol dioleic acid, propylene glycol dicapric acid, propyleneglycol di(capryl, capric acid), propylene glycol dicaprylic acid,neopentylglycol dicapric acid, neopentylglycol dioctanoic acid, glyceryltricaprylic acid, glyceryl triundecylic acid, glyceryl triisopalmiticacid, glyceryl triisostearic acid, octyldodecyl neopentanoic acid,isostearyl octanoic acid, octyl isononanoic acid, hexyldecyl neodecanoicacid, octyldodecyl neodecanoic acid, isocetyl isostearic acid,isostearyl isostearic acid, octyldecyl isostearic acid, polyglycerinoleanoic acid ester, polyglycerin isostearic acid ester, triisocetylcitric acid, triisoalkyl citric acid, triisooctyl citric acid, lauryllactic acid, myristyl lactic acid, cetyl lactic acid, octyldecyl lacticacid, triethyl citric acid, acetyltriethyl citric acid, acetyl tributylcitric acid, trioctyl citric acid, diisostearyl maleic acid, di2-ethylhexyl hydroxy stearic acid, 2-ethyl hexyl succinic acid,diisobutyl adipic acid, diisopropyl sebasinic acid, dioctyl sebacinicacid, cholesteryl stearic acid, cholesteryl isostearic acid, cholesterylhydroxy stearic acid, cholesteryl hydroxy stearic acid, cholesteryloleic acid, dihydrocholesteryl oleic acid, pitsteryl isostearic acid,pitsteryl oleic acid, isocetyl 12-stealoyl hydroxy stearic acid, stearyl12-stealoyl hydroxy stearic acid, isostearyl 12-stealoyl hydroxy stearicacid.

Preferable hydrocarbon oil described above may comprise squalene, liquidparaffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquidisoparaffin, polybuden, microcrystalline wax, vaselin and the like.

Preferable silicone oil may comprise polymethylsilicone,methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane,decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane-methyl cetyloxysiloxan copolymer, dimethyl siloxane-methylstealoxysiloxane copolymer, alkyl modified silicone oil, amino modifiedsilicone oil and the like.

Preferable fluoride oil can comprise perfluoropolyether and the like.

Preferable animal or plant oil can comprise avocado oil, almond oil,olive oil, sesame oil, rice husk oil, safflower oil, soy-bean oil, cornoil, rape oil, amygdalin oil, palm kernel oil, palm oil, pimaja oil,sunflower oil, fruite seed oil, cotton seed oil, coconut palm oil cucuinut oil, wheat embryo bud oil, rice embryo bud oil, sia butter,evening-primrose oil, marker daymia nut oil, medo home oil, egg yolkoil, lanolin, hempseed oil, mink oil, orange nippy oil, hohoba oil,carnawa wax, liquid lanolin, solid pimaja wax and the like.

Preferable humectants can comprise water-soluble low molecularhumectants, lipophilic low molecular humectants, water-soluble polymerand lipid soluble polymer.

Specifically, preferable water soluble low molecular humectants cancomprise cerin, glutamine, sorbitol, mannitol, pyrrolidone-carboxylicacid Na, glycerin, propylene glycol, 1,3-butylene glycol, ethyleneglycol, polyethylene glycol (polymerization index >2), polypropyleneglycol (polymerization index >2), lactic acid, lactate salt and thelike.

Preferable lipid soluble low molecular humectants can comprisecholesterol, cholesteryl ester and the like.

Preferable water-soluble polymer can comprise carboxy vinyl polymer,poly asparaginic acid salt, tragacanth, xanthin gum, HMC (hydroxy methylcelluose), HEC (hydroxy ethyl celluose), HPC (hydroxy propyl celluose),carboxymethylcellulose, water-soluble chitin, chitosan, dextrin and thelike.

Preferable lipid soluble polymer can comprisepolyvinylpyrrolidone-eicocene copolymer, polyvinylpyrrolidone-hexadecenecopolymer, nitrocellulose, dextrin fatty acid ester, silicone polymerand the like.

Preferable emollients can comprise long chain acyl glutamic acidcholesteryl ester, cholesteryl hydroxy stearic acid, 12-hydroxy stearicacid, rogic acid, lanolin fatty acid cholesteryl ester and the like.

Preferable surface-active agent can comprise nonionic surfactants,anionic surfactants, cationic surfactants, ambivalent surfactants andthe like.

Specifically, preferable non-ionic surfactants can compriseself-emulsified monostearic acid glycerin, propylene glycol fatty acidester, glycerin fatty acid ester, polyglycerin fatty acid ester,sorbitan fatty acid ester, polyoxyethylene (POE) sorbitan fatty acidester, POE sorbitan fatty acid ester, POE glycerin fatty acid ester, POEalkyl ether, POE fatty acid ester, POE solid pimaja oil, POE pimaja oil,POE-POP copolymer, POE-POP alkyl ether, polyether modified silicone,lauric acid alkanol amide, alkyl amine oxide, hydrogen addition soybeanphospholipid and the like.

Preferable anionic surfactants can comprise fatty acid soap, α-acylsulfonic acid salt, alkyl sulfonic acid salt, alkyl ally sulfonic acid,alkyl naphthalene sulfonic acid salt, alkyl sulfonic acid salt, POEalkylether sulfate salt, alkyl amide sulfate salt, alkyl phosphate salt,POE alkyl phosphate salt, alkylamide phosphate salt, alkyloylalkyltaurine salt, N-acyl-amino acid salt, POE alkyl ether carboxylic acidsalt, alkyl sulfo succinic aid salt, alkyl sulfo-acetic acid salt,acylated hydrolysable collagen peptide salt, perfluoro alkyl phosphateester and the like.

Preferable cationic surfactant can comprise alkyl trimethyl ammoniumchloride, stearyl trimethyl ammonium chloride, stearyl trimethylammonium bromide, setostearyltrimethyl ammonium chloride, distearyldimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride,vehenyltrimethyl ammonium bromide, benzalkonium chloride, diethylaminoethyl amide stearic acid, dimethylaminopropyl amide stearic acid,lanolin derivatives quaternary ammonium and the like.

Preferable ambivalent surfactants can comprise carboxy betaine type,amide betaine type, hydroxy sulfo betaine type, phosphpbetaine type,aminocarboxylic acid, imidazoline derivatives type, amide amine type andthe like.

Preferable organic and inorganic dyes can comprise silicic acid,anhydrous silicic acid, magnesium silicic acid, talc, ceracyte, mica,caolin, bengala, clay, bentonite, titan film mica, oxy chlorine bismuth,zirconium oxide, magnesium oxide, zinc oxide, titan oxide, aluminiumoxide, calcium sulfate, barium sulfate, magnesium sulfate, calciumcarbonate, magnesium carbonate, ferrous oxide, chromium oxide, chromiumhydroxide, calamine, carbon black and their complex thereof as aninorganic dyes; polyamide, polyester, polypropylene, polystyrene,polyurethane, vinyl resin, urea resin, phenol resin, fluoride resin,silicone resin, acryl resin, melamine resin, epoxy resin, polycarbonateresin, divinyl benzene-styrene copolymer, silk powder, cellulose, CIpigment yellow, CI pigment orange as an organic dyes; and their complexetc.

Preferable organic powder can comprise metal soap such as calciumstearate; alkyl phosphonate metal salt such as sodium zinc cetylic acid,zinc laurylic acid, calcium laurylic acid; acylamino acid polyvalentmetal salt such as calcium N-lauroyl-β-alanine, zincN-lauroyl-β-alanine, calcium N-lauroyl-glycine etc.; amide sulfonic acidpolyvalent metal salt such as calcium N-lauroyl-taurine, calciumN-palmitoyl-taurine; N-acyl basic amino acid such asNε-lauroyl-L-lysine, Nε-palmitoyl-lysine, Nα-palmitoyl ornitine,Nα-lauroly arginine, hardened lanolin fatty acid acyl arginine and thelike; N-acylpolypeptide such as N-lauroylglycyl glycine; α-amino fattyacid such as α-amino caprylic acid, α-amino lauric acid and the like;polyethylene, polypropylene, nylon, polymethylmetacrylate, polystyrene,divinylbenzene-styrene copolymer, ethylene tetrafluoride and so on.

Preferable ultraviolet absorbing agents can comprise paraaminobenzoicacid, paraamonoethyl benzoate, paraamino amyl benzoate, paraamino octylbenzoate, ethyleneglycol salicylate, phenyl salicylate, octylsalicylate, benzyl salicylate, butylphenyl salicylate, homomentylsalicylate, benzyl cinnamic acid, paramethoxy 2-ethoxy ethyl cinnamicacid, paramethoxy octyl cinnamic acid, diparamethoxy mono-2-ethylhexaneglyceryl cinnamic acid, paramethoxy isopropyl cinnamic acid,diisopropyl-diisopropyl cinnamate ester mixture, urokanic acid, ethylurokanic acid, hydroxy methoxy benzophenone, hydroxymethoxy benzophenonesulfonic acid and their salt, dihydroxy methoxy benzophenone, dihydroxymethoxy benzophenone disulfonate Na, dihydroxy benzophenone,tetrahydroxybenzophenone, 4-tert-butyl-4′-methoxydibenzoylmethane,2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine,2-(2-hydroxy-5-methylphenyl)benzotriazole and the like.

Preferable preservatives can comprise hinokitiol, trichloric acid,trichlorohydroxydiphenylether, chlorohexidine glucuronate,phenoxyethanol, resorcine, isopropylmethylphenol, azulene, salicylicacid, zinc pilithione, bezalconium HCl, photosensitizer 301,mononitroguaiacol Na, undecylenic acid etc.

Preferable antioxidants can comprise butylhydroxyanisole, propylgallate, ellisorbate and the like.

Preferable pH controller can comprise citric acid, sodium citrate, malicacid, sodium malate, fumaric acid, sodium fumaric acid, succinic acid,sodium succinic acid, sodium hydroxide, sodium hydrogen phosphate andthe like.

Preferable alcohol can comprise cetyl alcohol etc.

Furthermore, other ingredient addable to above described component andthe amount thereof is not limited within the scope of the purpose andeffect of the present invention, however, it is preferable that theamount of the other ingredients ranges from 0.01 to 5%, more preferably,0.01 to 3% in that of total composition.

The cosmetic composition of the present invention can be modified as asolution, emulsion, cohesive mixture etc.

Above described ingredients such as water-soluble vitamin, lipid solublevitamin, peptide polymer, polysaccharide polymer, sphingolipid, sea weedextract and addable ingredients which can be added other than abovedescribed ingredients if necessary, can be obtained by conventionalmethods disclosed in the literature (Matsumoto Mithio, Manual for thedevelopment of transdermal applied preparation. Seisi Press, 1^(st) Ed.,1985).

Additionally, the present invention also provides a cosmetic additivescomprising above described extract as an essential component forprevention or improvement of baldness disorder and seborrheic skindisease.

Above cosmetic additives can be used by adding to existing cosmetics andwashing solution to prevent, improve or treat baldness disorder andseborrheic skin disease.

Furthermore, above cosmetic additives can be used to cream, lotion,message pack, and body washing solution, soup, shampoo and the like.

Inventive extract of the present invention have no toxicity and adverseeffect therefore; they can be used with safe.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the compositions, use andpreparations of the present invention without departing from the spiritor scope of the invention.

The present invention is more specifically explained by the followingexamples. However, it should be understood that the present invention isnot limited to these examples in any manner.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

The above and other objects, features and other advantages of thepresent invention will more clearly understood from the followingdetailed description taken in conjunction with the accompanyingdrawings, in which;

FIG. 1 shows TLC photograph of the extracts and fractions of hardy kiwi;

FIG. 2 shows 2D-TLC photograph of [1] sub-fraction;

FIG. 3 shows 2D-TLC photograph of [2] sub-fraction;

FIG. 4 presents the lowering effect of hot-water extract of hardy kiwion the blood DHT concentration in mouse;

FIG. 5 presents the lowering effect of non-polar solvent soluble extractof hardy kiwi on the blood DHT concentration in mouse;

FIG. 6 presents the lowering effect of purified extract of hardy kiwi onthe blood DHT concentration in mouse;

FIGS. 7 and 8 show the photographs of mouse hair grown in its back areatreated with control and the hardy kiwi extract for two weeks orallyrespectively; and

FIG. 9 shows effects of extracts of hardy kiwi on the production of IL-4in RBL-2H3 cells.

BEST MODE FOR CARRYING OUT THE INVENTION

The following Examples and Experimental Examples are intended to furtherillustrate the present invention without limiting its scope.

EXAMPLE 1 Preparation of Hardy Kiwi Extract 1-1. Preparation of WaterExtract of Hardy Kiwi

100 g of dried fruit and dried stem of Actinidia arguta, dried fruit ofA. kolomikta, and dried fruit of A. polygama purchased from Kyung-dongMarket located in Seoul were crushed, mixed with 1 L of distilled waterand subjected to reflux extraction for 3 hrs at 90˜95° C. with threetimes and the extract was filtered with filter paper, concentrated usingby rotary evaporator (N-1000, Eyela Co. Japan) at 55˜65° C. underreduced pressure and dried with freezing dryer to obtain 15.6 g of driedfruit extract of Actinidia arguta, 10.4 g of dried stem extract ofActinidia arguta, 16.2 g of dried fruit extract of A. kolomikta and 17.0g of dried fruit extract of A. polygama. The powdered extract wasdissolved in distilled water (100 mg/ml) separately.

1-2. Preparation of Water-Alcohol Soluble Extract of Fruit of Hardy Kiwi

Except using various ratios of a water-alcohol solvent mixture such as30%, 50%, and 70% ethanol in water as an extraction solvent, in place ofwater, all the procedure was identical to those of Example 1-1. As aresult, 11 g˜13 g of dried extract of fruit of Actinidia arguta wereobtained at each ratio of the solvent mixtures and the each powderedextract was dissolved in distilled water (100 mg/ml).

EXAMPLE 2 Preparation of Polar Solvent and Non-Polar Solvent SolubleHardy Hardy Kiwi Extract

The water extract of dried fruit of Actinidia arguta prepared in Example1-1 was subject to fractionation by following procedure.

2-1. Preparation of Chloroform Soluble Fraction

50 ml of distilled water was added to 5 g of the fruit extract ofActinidia arguta obtained in Example 1-1. 50 ml of chloroform was addedthereto in separatory funnel, shaken vigorously to divide intochloroform soluble layer and water soluble layer I.

2-2. Preparation of Ethyl Acetate Soluble Fraction

Above water soluble layer I obtained in Example 2-1 was mixed with 50 mlof ethyl acetate and then divided into ethyl acetate soluble layer andwater soluble layer II.

Above chloroform soluble layer, ethyl acetate soluble layer and watersoluble layer II were concentrated by rotary evaporator, dried withfreeze dryer to obtain 0.34 g of chloroform soluble fraction, 0.05 g ofethyl acetate soluble fraction, and 4.61 g of water fraction powders,respectively.

EXAMPLE 3 Fractionation of Hardy Kiwi Extract by Silica Gel ColumnChromatography

2,784 mg of ethyl acetate soluble fraction in Example 2-2 was furthersubjected to silica gel column chromatography (Daiso gel IR-60-W-40: 63mm). The developing solvent was started with chloroform:methanol:water([1] 90:11:1, [2] 60:10:1, [3] 60:20:2) solvent mixture and ended withmethanol[4] with eluting speed of 300 ml/hr to obtain foursub-fractions([1] 2,381 mg, [2] 135 mg, [3] 148 mg, [4] 98 mg).

Above water extract, ethyl acetate soluble fraction and foursub-fractions were subjected to TLC (TLC plate: Merck Co. Ltd.,Developing solvent; chloroform: methanol:water=9:5:1) and the resultswere shown in FIG. 1. As shown in FIG. 1, lane 1 is water extract, lane2 is ethyl acetate soluble fraction, lane 3 is sub-fraction No.[4], lane4 is sub-fraction No.[4], lane 5 is sub-fraction No.[2] and lane 6 issub-fraction No.[1].

Above sub-fractions No.[1] and No.[2] were subjected to 2D-TLC usingchloroform:methanol:water (9:5:1) solvent mixture as a 1^(st) developerand chloroform: acetone:water (3:8:0.5) solvent mixture as a 2^(nd)developer (See FIG. 1 and FIG. 2).

EXPERIMENTAL EXAMPLE 1 Inhibiting Activity on the Formation of Blood DHT1-1. Effect of Polar Soluble Extract of Hardy Kiwi on the Concentrationof Blood DHT

To confirm the inhibition effect of hardy kiwi extract on theconcentration of blood DHT, the water extract and ethanol extract offruit of Actinidia arguta were administrated into mice and theconcentration of blood DHT were determined by following procedure;

Male C57BL/6 mice, aged 6 weeks (Seoul national university animalexperimental center) were acclimated to the environment for 1 week.After 1 week, 16 mice were divided into 4 groups and each group wasorally administered with 100 μl of the water extract of fruit ofActinidia arguta (1500 μg/mouse/day), 100 μl of the ethanol extract offruit of Actinidia arguta (1500 μg/mouse/day), 100 μl of finasteride(100 μg/mouse/day), and 100 μl of drinking water (100 μg/mouse/day) for3 weeks, respectively. After mice were sacrificed and the blood serumand spleen organ were collected therefrom, the concentration of bloodDHT was measured by ELISA (IBL-Hamburg GmbH) method.

As shown in the FIG. 4, the concentration of blood DHT in groupsadministered with extracts of fruit of Actinidia arguta showed adecrease of about 90% with similar to groups administered withfinasteride.

1-2. Effect of Non-Polar Soluble Extract Of Hardy Kiwi on theConcentration of Blood DHT

To measure the concentration of blood DHT of C57BL/6 mice, eachchloroform soluble fraction, ethyl acetate soluble fraction and watersoluble fraction II prepared in above Example 2 was subjected to theidentical experiment disclosed in above Experimental Example 1-1.

50 μg of the chloroform soluble fraction, ethyl acetate solublefraction, or water soluble fraction was administrated to C57BL/6 mice,separately. 100 μl of drinking water was administrated as control.

As shown in the FIG. 5, the concentration of blood DHT showed a decreaseby about 95% in the group administered with the ethyl acetate solublefraction from the extract of Actinidia arguta fruit and a slightdecrease in the group administered with the water soluble fraction fromthe extract of Actinidia arguta fruit. However, it was not affected inthe group administrated with the chloroform soluble fraction of hardykiwifruit.

1-3. Effect of Silica Gel Column Chromatography-Purified Fraction on theConcentration of Blood DHT

To measure the concentration of blood DHT of C57BL/6 mice, each ofsilica gel column chromatography-purified fractions [1], [2], [3] and[4] prepared in above Example 3 were subjected to the identicalexperiment disclosed in above Experimental Example 1-1.

Each of 30 μg of silica gel column chromatography fractions [1], [2],[3], or [4] was administrated to C57BL/6 mice, respectively. 100 μl ofdrinking water was administrated as control.

As shown in the FIG. 6, mouse administered with fraction [1] and [2]shows significantly inhibition of DHT.

1-4. Effect of Water Extract of Hardy Kiwi Stem on the Concentration ofBlood DHT

To measure the concentration of blood DHT of C57BL/6 mice, water extractof dried stem of Actinidia arguta was subjected to the identicalexperiment disclosed in above Experimental Example 1-1.

After 1 week, 8 mice were divided into 2 groups and each group wasorally administered with 100 μl of the water extract of dried stem of A.arguta (1500 μg/mouse/day) and 100 μl of drinking water (100μg/mouse/day) for 3 weeks, respectively. After mice were sacrificed andthe blood serum and spleen organ was collected therefrom, theconcentration of blood DHT was measured. In the group administered withthe water extract of dried stem of A. arguta, the concentration of bloodDHT was 142 pg/ml, 193 pg/ml, 362 pg/ml and 1625 pg/ml, respectively.Therefore, it confirmed that the extract of dried stem of A. arguta aswell as the extract of dried fruit of A. arguta showed an inhibitioneffect on DHT formation.

EXPERIMENTAL EXAMPLE 2 Stimulation Effect on the Formation of Hair Root2-1. Effect of Water Extract of Hardy Kiwi on the Formation of Hair Root

To confirm the effect of water extract of hardy kiwi on the formation ofhair root, mouse model was used as follows;

Female C57BL/6 mice aged 6 weeks (Seoul national university animalexperimental center) were acclimated to the environment for 7 days.After 1 week, the hair on the back of each mouse was carefully shavedusing electrical shaver. Then mice were divided into 2 groups and eachgroup was orally administered with 100 μl of the water extract of fruitof Actinidia arguta (1500 μg/mouse/day) and 100 μl of drinking water(100 μg/mouse/day) for 4 weeks, respectively. Whether hair root wasactivated or not can be easily recognized by confirming the change ofskin color where the hair was removed from bright red to darkened colorby melanin pigment. Also, the growth of hair can be determined byobserving directly the effect of water soluble extract of hardy kiwi onthe formation of hair root.

As shown in the FIGS. 7 and 8, the skin color of hair-removed region inthe group administered with the water extract of hardy kiwi, got darkenwithin 2 weeks after the administration, which showed the growing ofhair. However, the growth of hair as well as the change of skin colordid not showed in the group administrated with drinking water. At thetime of 4 weeks after administration, the back of each mouse in theformer group was covered with new hair, while that in the latter groupdid not showed any new hair yet. Therefore, it confirmed that the thewater extract of fruit of hardy kiwi can stimulate hair growth in themechanism of promoting the formation of hair root of mouse.

2-2. Effect of Non-Polar Solvent Soluble Extract of Hardy Kiwi on theFormation of Hair Root

To confirm the effect of chloroform soluble fraction, ethyl acetatesoluble fraction and water soluble fraction which were prepared in aboveExample 2, following experiments were subjected in similar procedure tothat disclosed in above Experimental Example 2-1.

Then mice were divided into 4 groups and each group was orallyadministered with 100 μl of the water soluble layer II of hardy kiwi,100 μl (50 μg) of the ethyl acetate fraction of hardy kiwi, 100 μl ofthe chloroform fraction of hardy kiwi or 100 μl of drinking water for 4weeks.

At the result, hair growth was stimulated significantly in the groupadministered with the ethyl acetate fraction of hardy kiwi compared withthose in the other groups.

EXPERIMENTAL EXAMPLE 3 Effect of Hardy Kiwi Extract on the Improvementof Seborrheic Skin Disorders

To test the effect of hardy kiwi extract on the improvement ofseborrheic skin disorders, each 1 g of water extract of fruit ofActinidia arguta was administered orally once a day for 4 weeks to threevolunteers suffered from seborrheic dermatitis to confirm whether theseborrheic skin disorder was improved or not as follows:

3-1. Patient K, a 29 year-old Korean female who had been suffered fromsevere skin seborrheication and lots of dandruffs to progress todepilation. After she had taken tablets containing 1 g of hardy kiwiwater extract once a day for 2 weeks, the seborrheic and keratogenousskin disorders was significantly reduced and the depilation syndromewere reduced to more than about 50%.

3-2. Patient P, a 27 year-old Korean male who had been suffered fromoily face and scalp and lots of dandruffs. After he had taken tabletscontaining 1 g of hardy kiwi water extract once a day for 2 weeks, theoily face was significantly alleviated and the alopecia was reduced tomore than about 70%.

3-3. Patient U, a 29 year-old Korean male who had been suffered fromseborrheic skin, especially, face and purutitic and spotty scalp fromseveral years ago. After he had taken tablets containing 1 g of hardykiwi water extract once a day for 2 weeks, the purutitic syndrome ofscalp was disappeared and the trouble caused by oily face, for example,pimple, was also disappeared significantly.

EXPERIMENTAL EXAMPLE 4 Effects of Extracts from A. Arguta, A. Kolomiktaand A. Polygama on the Production of IL-4 in RBL-2H3 Cells

It is known that lymphocytes from patients with seborrheic skin disorderproduce more TH2-type cytokines than TH1-type cytokines (Neuber et al.,Arch. Dermatol. Res., pp 532-536, 1996; Ashbee et al., Exp. Dermatol.,pp 106-112, 1994; Bergbrant et al., Clin. Exp. Dermatol., pp 402-406,1999; Parry and Sharpe, Br. J. Dermatol., pp 254-263, 1998; Bergbrant etal., Clin. Exp. Dermatol., pp 331-338, 1991). Among TH2-type cytokines,IL-4 was known to increase a production level in skin lesions from SDpatients (Faergemann et al., Br. J. Dermatol., pp 549-556, 2001). AlsoIL-4 was known to induce apoptosis in cultured human follicularkeratinocytes and inhibit hair growth (Mandt et al., Eur. J. Dermatol.,pp 432-438, 2002).

To compare the effect of hardy kiwi extracts on the production of IL-4,A23187-stimulated RBL-2H3 cells were used as follows;

RBL-2H3 (Rat mast cell line, ATCC No: CRL-2256) were cultured in 24 wellplates in MEM supplemented with 10% FBS, 2 mM L-glutamine, 10 mM HEPES,1 mM sodium pyruvate, 50 μg streptomycin, and 100 U/ml penicillin (allfrom Life Technologies, USA) at 37° C. under 5% CO₂. Cells were treatedwith A23187 (1 μg/ml, Sigma, USA) and A. arguta, A. kolomikta or A.polygama extracts (1 mg/ml). After 12 hrs culture, the supernatants werecollected to measure the level of IL-4 by ELISA (rat IL-4 ELISA kit, R&Dsystems, USA) and the results were expressed as percentage of inhibitoryactivity on A23187-mediated IL-4 production.

As shown in FIG. 9, the extract of A. arguta, A. kolomikta and A.polygama decreased the A23187-mediated production of IL-4 indose-dependent manners. But there was no difference of extracts onreduction of IL-4.

EXPERIMENTAL EXAMPLE 5 Toxicity Test

To examine the toxicity of the extract of hardy kiwi, repetitivetoxicity tests were performed on mouse.

The female of Balb/c mice were divided with 2 groups and inventive waterextract of Actinidia arguta fruit (150 mg/kg) was administered to themice at 150 mg/kg for 4 weeks and water was treated to the controlgroup. The symptom of toxicity was observed for 4 weeks such as thechange of weight, the hematological analysis and histological test.

As a result of experiment, there was no death example of the miceadministered with 150 mg/kg inventive hardy kiwi extract and there wasno significant abnormality in the gain or loss of weight, the caloricintake of feed, the hematological analysis and the histological testetc. In accordance with above results, it was confirmed that the hardykiwi extract was safe to take orally as a medicine.

-   -   (1) Weight and observation: the unusual change of weight was not        observed.    -   (2) Hematological analysis: No abnormal symptom was observed in        the number of WBC, lymphocyte, monocyte, neutrophil, eosinophil,        basophil, RBC, hemoglobin and platelet.    -   (3) Serum biochemical test: No abnormal symptom was observed in        the level of AST, ALT, LDH, bilirubin, creatinine, glucose,        cholesterol, minerals, albumin, BUN, lipase and amylase of        serum.    -   (4) Histological test: No abnormal symptom was observed in the        tissue of kidneys, the spleen, the liver and the thymus.

Hereinafter, the formulating methods and kinds of excipients will bedescribed, but the present invention is not limited to them. Therepresentative preparation examples were described as follows.

Preparation of Injection

Water extract of hardy kiwi in Example 1 50 mg Sodium metadisulfite 3.0mg Methylparaben 0.8 mg Propylparaben 0.1 mg Distilled water forinjection optimum amount

Injection preparation was prepared by mixing above components and making2 ml by the conventional method and then filing filling all thecomponents 2 ml ample and sterilizing by conventional injectionpreparation method.

Preparation of Tablet

Water extract of hardy kiwi in Example 1 50 mg Corn Starch 100 mgLactose 100 mg Magnesium Stearate 2 mg

Tablet preparation was prepared by mixing above components andentabletting.

Preparation of Capsule

Water extract of hardy kiwi in Example 1 100 mg Corn starch 100 mgLactose 100 mg Talc 2 mg Magnesium Stearate optimum amount

Tablet preparation was prepared by mixing above components and fillinggelatin capsule by conventional gelatin preparation method.

Preparation of Liquid

The 70% ethanol extract of hardy kiwi 100 mg Sugar 20 g Fructose 20 gLemon flavour optimum amount Distilled water 100 ml

Liquid preparation was prepared by mixing above components and thenfilling 100 ml brown bottle sterilizing by conventional liquidpreparation method.

Preparation of Health Care Food

Water extract of hardy kiwi in Example 1 1000 mg Vitamin mixture 20 g Vitamin A acetate 70 μg  Vitamin E 1.0 mg  Vitamin B₁ 0.13 mg  VitaminB₂ 0.15 mg  Vitamin B₆ 0.5 mg  Vitamin B₁₂ 0.2 μg  Vitamin C 10 mg Biotin 10 μg  Amide nicotinic acid 1.7 mg  Folic acid 50 μg  Calciumpantothenic acid 0.5 mg Mineral mixture optimum amount  Ferrous sulfate1.75 mg  Zinc oxide 0.82 mg  Magnesium carbonate 25.3 mg  Monopotassiumphosphate 15 mg Dicalcium phosphate 55 mg Potassium citrate 90 mgCalcium carbonates 100 mg Magnesium chloride 24.8 mg

The above-mentioned vitamin and mineral mixture may be varied in manyways. Such variations are not to be regarded as a departure from thespirit and scope of the present invention.

Preparation of Health Beverage

Water extract of hardy kiwi in Example 1 1000 mg Citric acid 100 mgOligosaccharide 100 g Apricot concentration 2 g Taurine 1 g Distilledwater 900 ml

Health beverage preparation was prepared by dissolving active component,mixing, stirred at 85° C. for 1 hour, filtered and then filling all thecomponents in 2000 ml ample and sterilizing by conventional healthbeverage preparation method.

Preparation of Skin Lotion

Water extract of hardy kiwi in Example 1 1.00(%) Glycerol 3.00 Ethanol1.00 Propylene glycol 0.10 Flavour trace amount Distilled water made to100%

Skin preparation was prepared by dissolving active component accordingto conventional lotion preparation method.

Preparation of Lotion

Water extract of hardy kiwi in Example 1 3.00(%) L-ascorbicacid-2-magnesium phosphate 1.00 Soluble collagen (1% solution) 1.00Sodium citric acid 0.10 Citric acid 0.05 1,3-butylene glycol 3.00Distilled water made to 100%

Lotion preparation was prepared by dissolving active component accordingto conventional lotion preparation method.

Preparation of Cream

Water extract of hardy kiwi in Example 1 3.00(%)Polyethyleneglycomonosterate 2.00 Monostearate glycerin 1.00 Cetylalcohol 4.00 Squalene  .00 Tri 2- glyceryl ethylhexanoate 6.00Sphingo-glycolipid 1.00 1,3-butylene glycol 7.00 Distilled water made to100%

Preparation of Pack

Water extract of hardy kiwi in Example 1  5.00(%) Polyvinyl alcohol13.00 L-ascorbic acid-2-magnesium phosphate  1.00 Lauroylhydroxyproline 1.00 Soluble collagen (1% solution)  2.00 1,3-butylene glycol  3.00Ethanol  5.00 Distilled water made to 100%

Pack preparation was prepared by dissolving active component accordingto conventional pack preparation method.

Preparation of Beauty Solution

Water extract of hardy kiwi in Example 1  2.00(%)Hydroxyethylenecellulose (2% solution) 12.00 Xanthin gum (2% solution) 2.00 1,3-butylene glycol  3.00 Conc. Glycerin  4.00 Sodium hyaluronate 5.00 Distilled water made to 100%

Beauty solution preparation was prepared by dissolving active componentaccording to conventional beauty solution preparation method.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the present invention, and allsuch modifications as would be obvious to one skilled in the art areintended to be included within the scope of the following claims

INDUSTRIAL APPLICABILITY

As described in the present invention, an extract of the hardy kiwiprepared by inventive preparation reduced blood DHT level, promoted theformation of hair root in mouse model experiment, and inhibited thefalling out of hair and improved seborrheic skin disease of volunteerssuch as keratigenous skin, seborrhea etc. Accordingly, the extract ofhardy kiwi can be used as a pharmaceutical composition for thetreatment, improvement or prevention of baldness disorder or seborrheicskin disease. Furthermore, an extract of the hardy kiwi can be used as aform of heath care food, food additives, feed additives or cosmeticcomposition.

What is claimed is:
 1. A method for treating or improving seborrheicskin disease or stimulating hair growth comprising administering aneffective amount of a lower alcohol extract of Actinidia arguta fruit toa mammal in need thereof.
 2. The method according to claim 1, whereinsaid extract is administered in a form of a pharmaceutical compositionwhich comprises said extract in an amount ranging from 0.01 to 50% byweight based on the total weight of the formulation and apharmaceutically acceptable carrier.
 3. The method of claim 1, whereinthe mammal is human.
 4. The method according to claim 1, which comprisesorally administering a composition comprising the effective amount ofsaid extract of Actinidia arguta fruit.
 5. The method according to claim1, which comprises topically applying a composition comprising theeffective amount of said extract of Actinidia arguta fruit to thesurface area which is in need of the treatment, of the mammal.